Through the process of homeostasis, the immune system maintains a certain number and repertoire of T and B lymphocytes, collectively referred to as an individual's “immune repertoire.” An individual's immune repertoire constantly changes, however, as a result of continuous cell turnover and the exposure to antigens. Such immune repertoire changes may include, for example, the generation of new (naive) T and B lymphocytes, expansion of active T and B lymphocytes, and the formation of new memory T and B lymphocytes.
Immune therapies and cellular therapies are becoming increasingly popular tools for the treatment of cancer and autoimmune disease. Immune therapies may include antibody treatments to modulate immune pathways or to boost a patient's immune response to a disease. Cellular therapies may include exposing a patient's blood or white blood cells to a disease antigen ex vivo and subsequently reintroducing the treated blood or white blood cells to the patient. While conventional methods utilize synthetic small molecules to target particular disease pathways, immune therapies and cellular therapies may act by educating a patient's immune system to fight disease.
When in a disease state, or during treatment of such disease state, a patient's immune system mobilizes to fight the disease. As a result, the turnover rate of the immune repertoire may change. A measurement of such change may give an indication of the effectiveness of the treatment. Currently, however, no tools or methods are available which would allow scientists or physicians to measure the immune repertoire turnover rate; current methods, such as white blood cell counts and flow cytometry, are not ideal. Measuring a patient's white blood cell count provides only the total number of lymphocytes or the number of cells that belong to lymphocyte category, and flow cytometry allows classification of T and B lymphocytes based on surface markers. Neither of these methods, however, provides an accurate measurement of the immune repertoire turnover rate. As such, current methods are not ideal for the evaluation of therapeutic results of therapies, such as immune therapies, the generation of markers for pre-screening patients, and the identification of those patients best fit for a particular therapy. What is needed, therefore, is a tool to classify T and B lymphocytes at the single cell level based on the differentially-expressed T or B lymphocyte receptors and a method of utilizing this information to determine a change in an individual's immune repertoire.